It is well-known to use sample handling systems to store and retrieve high numbers of samples in automated sample libraries. A sample may be, for example, an aliquoted and/or diluted chemical or biochemical compound solved in dimethyl-sulfoxide (DMSO), or a biological sample, and the libraries of these samples are contained in a frozen state in a humidity controlled cold-room in freezers at −20° C. or −80° C. The samples retrieved from the cold room can then—after thawing—directly be used for high-throughput screening (HTS) of substances for their activity on specific biological targets of interest, or for biological studies or assays, as this may be performed in the drug discovery process.
A compound handling system of this type which is capable of handling a multiplicity of chemical or biological samples is known from U.S. Pat. No. 6,827,907 B2 and comprises a single piece storage plate which has a grid-like arrangement of separation walls defining 384 rectangular storage compartments. The 384 storage compartments are configured and dimensioned to hold a corresponding number of micro-tubes. The storage compartments are open to the top and the bottom to form through holes for receiving the micro-tubes. After filling the samples into the micro-tubes all micro-tubes arranged in the compartments of the storage plate are covered with a sealing foil which is then sealed to the upper edges of the micro-tubes. Thereafter, the foil is punched around the micro-tubes so as to remove those parts of the foil arranged in the space between the micro-tubes to make all 384 micro-tubes individually accessible. In order to allow retrieval and processing of individually composed compound subsets from the large sample libraries, the respective samples are pushed from the storage compartments of the respective storage plates through the open bottom thereof into the compartments of a delivery plate arranged beneath the storage plate, so that the delivery plate then comprises the respective individually composed compound subset.
Taking into consideration that such compound libraries may comprise up to several millions of individual samples, known sample handling systems suffer from the disadvantage that due to the corresponding large number of storage plates much storage space is required in the cold room. Due to standardization of micro-plates, the outer dimensions of the storage plates cannot be changed. Accordingly, it is not possible to increase the number of storage compartments on the micro-plates through an increase of the outer dimensions of the micro-plates. Increasing the number of individual compartments on micro-plates with standardized outer dimensions by simply reducing the dimensions of the individual compartments of the grid may lead to compartments bounded by side walls having a wall thickness which may be too small to provide a mechanically stable support for the tubes in the micro-plate. For example, if the capacity of the conventional tube micro-plates having 384 compartments (16×24) would have to be increased, a micro-plate having increased capacity while maintaining the area where the compartments for receiving the tubes are arranged and while maintaining the arrangement of the compartments would need 1536 compartments ([2×16]×[2×24]=1536). This would result in a tube micro-plate having too small a wall thickness to provide adequate support for the tubes to be received in the compartments and for the means for punching the tubes through the open bottom of the compartments of the storage plate into corresponding compartments of a delivery plate (see further above).
Another problem connected with “downsizing” of the individual compartments of micro-plates with standardized outer dimensions is related to the manufacturing of such micro-plates, since micro-plates are typically injection-molded from a suitable molding material (e.g. an injection-moldable plastic). The reduced thickness of the side walls of the compartments can then no longer be reliably manufactured by injection-molding, since the injection-moldable material is not capable of being reliably injected into the very small spaces of the mold that correspond to the side walls of reduced wall thickness (of a 1536 compartments tube micro-plate). On the other hand, manufacturing the micro-plates by injection-molding is important as injection-molding is a manufacturing technique which is very reliable and cost-effective with respect to mass-manufacturing. In this respect, it has to be taken into consideration that high numbers of micro-plates are needed for the compound libraries.